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[Compliance of patients undergoing thromboprophylaxis with enoxaparin : The COMFORT study.]
Abstract
Venous thromboembolism and subsequent pulmonary embolism are frequent and sometimes fatal complications in patients after surgical interventions. To prevent thromboembolisms an effective prophylaxis is necessary and outpatients in particular need adequate compliance. The aim of the prospective non-interventional study COMFORT was to analyze 8,091 outpatients after surgical and orthopedic interventions with different risk profiles with respect to factors affecting patient compliance in a positive or negative way. The follow-up period was 14 days and 92.5 % of the patients took the medication for the prescribed duration, 2.1 % (n = 166) terminated the medication too early and no information was available for 5.9 % (n = 442) of the patients. The reasons given for the premature termination of the injections were no more need for prophylaxis and end of medication by order of the physician due to mobilization or adverse events. Of the patients 73 % stated that the administartion was simple and without any problems and the majority of patients recognized injection as the administration mode of low molecular weight heparin to be the most important medication. The findings of this study can contribute to a better understanding of patient compliance.
... Similar studies reported non-adherence rates of 4.3% -39.1% [14] [16]- [20] [27]- [31]. Assuming that our patients were honest, they might not have disposed all syringes in their sharps collector, they might have interpreted a 10-day course as a 10-day postoperative and not 10-day ambulatory treatment, they might have administered 40 rather than 42 syringes in a 6-week course for practical reasons (=4 packages) [28], or the prescription of one package (= 10 syringes) did not necessarily mean that all of them had to be injected. It illustrates that the syringe count was not very reliable, though the only way to objectively determine non-adherence. ...
... The overall adherence rate was high with an overall mean of 95.8%. Patients seem to have concerns with pre-filled syringes [14], but are aware of their need [28]. In further research, we propose investigating the relation between concerns and needs of those injecting LMWH (pre-filled syringes) and those taking new oral antithrombotic drugs (direct factor Xa or thrombin inhibitors), as with oral medication, much lower adherence rates of about 50% are reported [32] [33]. ...
Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s.c. self-injections of low-molecular-weight heparins (LMWH) is unknown.
Our objective was to provide a standard operating procedure (SOP) for community pharmacists and to compare pharmaceutical vs. standard care in both clinical and daily life settings.
We hypothesized that: pharmaceutical care results in improved adherence, safety, and satisfaction, and in fewer complications; the interventions used are feasible in daily life; and the results achieved in clinical and daily life settings are comparable.
In the clinical setting (randomized controlled trial), patients were recruited sequentially in hospital wards; in the daily life setting (quasi-experimental design with a comparison group), recruitment took place in community
pharmacies by pharmacists and trained master students during their internship. Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment.
The main outcome measures were: scores to assess patient’s skills; syringe count to assess adherence; and frequency, effectiveness, and patient’s assessment of received interventions.
The results show a median age of the 139 patients of 54 years. Interventions resulted in improved application quality (p < 0.01) and knowledge (p = 0.03). Oral instructions were pivotal for improving patients’ application quality. We found no significant score differences between the intervention groups in the clinical and daily life settings. Patients’ baseline skills were high, with the lowest score being 0.86 (score range −2.00 to +2.00). Adherence rate was high (95.8%).
In conclusion, our SOP for pharmacist interventions was of good quality, adequate, appreciated, and feasible in daily life. Patients are capable of managing s.c. injection therapies if adequate assistance is provided.
... The SALTO study found that adherence to and satisfaction with the oral thromboprophylaxis were better than for drop by injection in the context of outpatient's prolongation (Peidro-Garces et al. 2013). Several studies demonstrated that the prescription of rivaroxaban could afford a superior patient compliance compared with subcutaneous LMWH or enoxaparin (Carrothers et al. 2014;Rubenacker et al. 2013;Rogers et al. 2010). And Wilke's survey revealed the patients appeared to have a positive preference for oral thromboprophylaxis after major orthopedic surgery (Wilke 2009). ...
Objective
Venous thromboembolism (VTE) is major problem after hip fracture surgery with substantial morbidity and mortality. This study aimed to assess the postoperative compliance of thromboprophylaxis in elderly patients undergoing hip fracture surgery and to confirm the correlation between compliance and VTE risk. Methods
This retrospective cohort study included consecutive elderly hip fracture patients who undergoing surgery. According to the thromboprophylaxis regimens, patients were divided into non-compliant group (<14days), poor compliant group (14–27days) and good compliant group (≥28days). The primary outcome was the incidence of symptomatic DVT, PE within 6weeks postoperatively. ResultsBetween 2008 and 2012, 1214 eligible patients were included in this study. 761 (64.7%) patients were non-compliant, 224 (19.0%) patients were poor compliant, and 192 (16.3%) patients were good compliant. The overall VTE rate was 7.9% (73/1177), PE rate was 0.3% (4/1177). The VTE rate in good compliant group was lowest among three groups (4.2 vs. 5.4 vs. 9.6%, P=0.013), but the PE rates showed no significant differences (0 vs. 0.9 vs. 0.3%, P=0.241). The multivariate analysis showed that non-compliance was an independent risk factor of suffering VTE undergoing hip fracture surgery. Conclusions
In this study we found fewer than 1 in 5 patients maintained compliant with thromboprophylaxis guidelines after discharge following hip surgery. This is particularly concerning because those who were non-compliant had a higher risk of VTE postoperatively compared with those who were good compliant.
... Though the standard of care for thromboprophylaxis in TKA at the time of this study was enoxaparin, even with its acceptable safety and efficacy profile, [6] there was still need to improve patient compliance, the safety profile and mode of administration. [15] As stated by Pocock, one of the fundamental rules is that phase III trials are comparative. [16] To achieve the objective, rivaroxaban (new anticoagulant) was compared with enoxaparin (standard care anticoagulant) and establish the safety and efficacy profile of the new agent. ...
Venous thromboembolism is a significant cause of mortality and morbidity in patients following major orthopaedic surgeries. The RECORDS 3 trial revolutionised anticoagulation practice especially in patients with total knee arthroplasty and challenging the strong hold of warfarin and heparin in anticoagulation practice. With all these novel agents shifting the paradigm in anticoagulation management, Cost, in accessibility and lack of awareness of the availability of the agents amongst clinicians and surgeons alike are some factors militating against the use of these agents in patients in resource poor countries.
... Таким образом, врачами часто переоценивается фактор ЛП и недооценивается важность полного информирования пациента о преимуществах и необходимости назначаемой терапии. По результатам исследования [9] даже парентеральное введение препарата (изучалась приверженность пациентов, перенесших хирургическое вмешательство, терапии эноксапарином для профилактики тромбоэмболий) для 73% больных не является препятствием к выполнению врачебных назначений, если пациент понимает важность этого назначения. ...
Aim. Using the data from the PROFILE Registry and the patients’ questionnaire survey, to analyse the patients’ compliance with medical recommendations on lipid-lowering therapy (LLT).
Material and methods. Over the period from May 1st 2011 to December 31st 2011, 274 patients were included in the PROFILE Registry: 82 were referred to a specialised medical centre for the first time (control group, CG); 167 were regularly attending the medical centre (main group A, MGA); and 25 last visited the centre >2 years ago (main group B, MGB). 262 patients completed a questionnaire on the therapy compliance, while 12 refused to participate in the questionnaire survey.
Results. According to the results of the questionnaire survey, MGA patients were better informed about the LLT goals (65%) than their CG and MGB peers (35% and 48%, respectively; p<0,0001). The percentage of patients who took statins every day was 87% in MGA vs. 41,5% in CG and 64% in MGB (p=0,002). Statin therapy effectiveness was controlled regularly in MGA: cholesterol (CH) levels were measured every 6 months in 37,5% and every 12 months in 28%. For CG, these figures were 17% and 16%, while for MGB, they were 15% and 40%, respectively (p<0,0001). One-third of CG patients, every fourth MGB patient, and only 13% of MGA patients did not control their CH levels (p<0,0001).
Conclusion. The MGA patients who were regularly attending the State Research Centre for Preventive Medicine were the most LLT-compliant: they were well-informed about their disease and therapy goals, were regularly taking prescribed medications (statins), and had better treatment control and the highest LLT effectiveness.
Background:
Telemedicine technology is widely used especially after the COVID-19 pandemic. It can be used to give medical advice as well as follow up with the patients at home in the outpatient setting. Low molecular weight heparin, such as enoxaparin, decreases the risk of venous thromboembolism after cesarean delivery.
Objective:
assessing postcesarean women's adherence and experience to enoxaparin thromboprophylaxis regimens in the outpatient setting via telephone calls.
Methods:
prospective cohort study was conducted in the Maternity and Children Hospital (MCH). Postcesarean women were interviewed at the postnatal ward in the MCH. The participants were followed up for 10 days of the delivery to assess their adherence to and experience with enoxaparin thromboprophylaxis. Suboptimal adherence was defined as the missing of one or more doses of enoxaparin.
Results:
170 women participated in this study. The majority of them (78.8%) were fully adherent to enoxaparin while 21.2% missed at least one dose. The most-reported causes for suboptimal adherence were perceived lack of necessity (44.4%), forget to take the injection (30.6%), feeling of high load going to the primary care unit to take injection (27.8%), and fear of injection (11.1%).
Conclusion:
Telemedicine technology could be used to assess patients' adherence. The study results showed that the majority of participants were fully adherent to postcesarean enoxaparin but more than 20% of the participants were suboptimal adherent. Proper patient education techniques could influence patients' adherence and potentially decrease the risk of DVT in those populations.
Introduction
Extended outpatient chemoprophylaxis (ECP) following radical cystectomy (RC) for bladder cancer is proven to reduce rates of venous thromboembolism (VTE). While ECP is commonly performed with enoxaparin, its cost-effectiveness and adherence rate has been called into question. Data from orthopedic literature suggest that ECP with direct oral anticoagulants (DOACs) may be as effective in VTE prevention as enoxaparin in patients undergoing joint surgery. Our goal is to determine how urologic oncologists employ ECP following RC.
Methods
Members of the Society of Urologic Oncology were surveyed on practice patterns for the use of ECP after RC. Specific questions were asked regarding the use of inpatient and outpatient VTE prophylaxis, as well as perceived barriers to DOACs and enoxaparin.
Results
There were 121 of 878 (13.8%) respondents and the majority were in academic practices (83%). Most respondents had at least 5 years of experience and performed greater than 10 cystectomies annually. Almost all participants utilized inpatient (97%) and extended (80%) chemoprophylaxis for VTE prevention. Of those who elected for ECP, almost all (96%) used enoxaparin. Only 3 respondents (3%) prescribed oral agents such as rivaroxaban (2) or warfarin (1). Among those using enoxaparin, financial-specific barriers to treatment such as lack of insurance coverage (38%), inability to afford the medication (51%), and need for additional insurance authorization (44%) were reported. Poor patient adherence and refusal to perform injections were reported by 20% and 18% of respondents, respectively. Among the 23 physicians who did not use ECP, cost (39%) and delivery method (26%) were cited as barriers to treatment.
Conclusions
The majority of surveyed urologic oncologists are prescribing subcutaneous enoxaparin ECP following RC. Poor patient adherence due to self-injections and financial barriers were frequently reported and represent a possible opportunity for the use of oral anticoagulants in the post-operative setting. These data will be used in the development of a proposed clinical trial of a DOAC in the post-RC setting.
Aims
We translated the ABC adherence taxonomy (i.e. 7 terms and their corresponding definitions) published by Vrijens et al. (2012) into French and German without changing the original meaning with the aim to promote a standardised taxonomy for medication adherence to French‐ and German‐speaking researchers and clinicians.
Methods
A Delphi survey was performed. To generate round 1, we identified French and German synonyms for the 7 adherence terms through a literature search in PubMed. Investigators translated the original English definitions into French and German. Panellists were members of ESPACOMP—the International Society for Patient Medication Adherence; experts suggested by ESPACOMP members and first authors of medication adherence publications in French and German. Google forms were used to create online questionnaires. Delphi rounds were performed until consensus was reached. The consensus was defined according to the acceptance rate as moderate consensus (50–75%), consensus (>75–95%), and strong consensus (>95%).
Results
The literature search resulted in 4–6 (French) and 4–7 (German) items per English term. Delphi rounds were launched between November 2016 and April 2018. Three rounds sufficed to reach consensus on all terms and definitions from 26 French‐speaking and 25 German‐speaking panellists. Preferred terms for medication adherence are adhésion médicamenteuse (82%) in French and Medikamentenadhärenz (88%) in German.
Conclusion
The use of a common terminology for medication adherence with translations in French and German will contribute to standardise the vocabulary, to harmonise research projects and ultimately ease comparison of study results among researchers and clinicians.
Introduction
Current National Institute for Health and Care Excellence (NICE) guidelines recommend the use of Low Molecular Weight Heparin (LMWH) for one month post-operatively in abdominal and pelvic cancer surgery to reduce risk of venous thromboembolism. We audited the prescription of LMWH at discharge and the compliance of patients with LMWH post-operatively and instigated measures to improve compliance.
Materials and Methods
All patients undergoing major urological surgery from November 2011 to April 2012 were audited, with data collected on evidence of post-operative prescription (from discharge summaries). Patients within this 3-month period were questioned regarding compliance following discharge. Following this, changes were instigated to improve compliance (earlier discussion of post-operative LMWH administration in clinic, improved patient and junior doctor education). All patients undergoing surgery from November 2012 to June 2013 were identified and a re-audit completed.
Results
Post-operative prescription of LMWH improved overall from 73% to 88%. Patient compliance to complete LMWH course improved from 23% to 88%. At re-audit, 97% of patients felt that training was adequate, and 94% of patients understood the rationale for taking LMWH at re-audit.
Conclusion
Education of junior doctors improved prescription of LMWH at discharge. Improved patient education improves community LMWH use compliance post-discharge.
Prescription of postnatal thromboprophylaxis has increased with the Royal College of Obstetricians and Gynaecologists and the National Institute for Health and Care Excellence guidance. Our study of postnatal women meeting the criteria for thromboprophylaxis aimed to ascertain compliance with low-molecular-weight heparin and barriers to completion of a full course. Women were recruited from the antenatal clinic or postnatal wards. Those who agreed were contacted by telephone 14 days after delivery and asked about their compliance with and experience of thromboprophylaxis. 111 women were followed up. We found reported compliance with postnatal thromboprophylaxis to be high (83% taking the full course); most women self-injected (54%) but a significant number relied on family members (39%). Most would be prepared to take the course in a future pregnancy (94%); however, some felt that they needed more information. Reported compliance with postnatal thromboprophylaxis is high. This may be down to the motivation of the new mother, appropriate information giving and access to health care professionals for advice.
The purpose of this study was to examine the incidence and predictors of venous thromboembolism following body contouring.
The authors reviewed the American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2012 for all body contouring cases. A multivariate logistic regression was performed to determine predictors of venous thromboembolism, and used to define risk scores for each significant predictor.
Seventeen thousand seven hundred seventy-four patients underwent body contouring during the study period. Venous thromboembolism occurred in 99 individuals (0.56 percent). Multivariate logistic regression revealed that age older than 45 years [45 to 60 years (OR, 1.54; p = 0.1); older than 60 years (OR 3.1, p < 0.001)], undergoing contouring of the trunk (OR, 2.75; p < 0.001), obesity [body mass index of 30 to 34.9 (OR, 3.35; p < 0.001); body mass index of 35 to 39.9 (OR, 4.41; p < 0.001); body mass index ≥ 40 (OR, 3.14; p = 0.001)], and admission on an inpatient basis (OR, 3.01; p < 0.001) were associated with increased odds of venous thromboembolism. Patients' total scores were categorized as low (0 to 4), medium (5 to 7), or high risk (8 to 9). The low-risk cohort exhibited a venous thromboembolism incidence of 0.14 percent, the medium-risk cohort experienced an incidence of 0.97 percent, and the high-risk group experienced a venous thromboembolism incidence of 2.95 percent.
This study identifies predictors of venous thromboembolism and creates a simple risk-scoring model using a large, prospective data set. The authors' analysis demonstrates that in the presence of certain risk factors, the incidence of venous thromboembolism increases dramatically; in these cases, venous thromboembolism prophylaxis may be warranted.
Risk, III.
Transition from the hospital into the outpatient setting is a critical event for the appropriate provision of VTE prophylaxis. Data for this transition for the situation in Germany is scant. This was a retrospective, observational study in patients receiving in-hospital thromboprophylaxis and discharged with or without a recommendation to continue. Patient with previous thromboembolism were excluded. A total of 3,211 patients were identified by 518 physicians of which 2,853 had all data available for the present analysis; mean patient's age was 57.4 ± 17.5 (SD) years, 48.2 % were male and bodyweight was 79.8 ± 16.1 kg. During hospitalization 95.5 % of surgical and 84.0 % of medical patients received any thromboprophylaxis, the mean hospital duration being 12.7 ± 20.3 days. Surgical patients had high, medium and low risk in 53.8, 37.1 and 9.1 %, respectively. Medical patients had high, medium and low risk in 78.8, 19.8 and 1.4 %. A hospital recommendation to continue thromboprophylaxis was given to 84.6 % (95 % CI 83.1-85.9 %) of surgical and 64.9 % (95 % CI 59.1-70.6 %) of medical patients and implemented in 96.6 and 94.3 %, respectively. On the other hand, in patients without a respective hospital recommendation (15.4 % of surgical and 35.1 % of medical patients), thromboprophylaxis was continued in 65.3 % of surgical and 73.1 % of medical patients because of high risk. Our data illustrate acceptable rates of prophylaxis in surgical and medical patients in Germany. As the results show, it is essential that not only hospital physicians are aware of the actual risk at discharge, but office based physicians assess thromboembolic risk.
The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA) treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.
The evaluation of the efficacy of medication is confounded when patients do not adhere to prescribed regimens. Overdosing, underdosing, and erratic dosing intervals can diminish drug action or cause adverse effects. Using a new method with epilepsy as a model, we assessed compliance with long-term medications among newly treated and long-term patients. Medication Event Monitor Systems (Aprex Corporation, Fremont, Calif) are standard pill bottles with micro-processors in the cap to record every bottle opening as a presumptive dose. Compliance rates averaged 76% during 3428 days observed: 87% of the once daily, 81% of the twice daily, 77% of the three times a day, and 39% of the four times a day dosages were taken as prescribed. Coefficients of variation of drug serum concentrations had no significant relationship to compliance rates. Pill counts overestimated compliance increasingly as compliance with the prescribed regimen declined. Neither drug serum concentrations nor pill counts would have identified the frequency of missed doses that were revealed with continuous dose observations.
By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.
This study examines NIDDM patients' attitudes toward insulin injections, the basis of these attitudes, and how they may affect patients' willingness to take insulin.
Forty-four low-income Mexican American NIDDM patients were interviewed using open-ended in-depth interviewing techniques. Transcripts were analyzed using techniques of content analysis. Data classification was cross-checked in analysis conferences and through a second researcher coding 50% of the cases, comparing the results, then resolving any discrepancies.
Patients' positive attitudes toward insulin focus on its efficacy and efficiency, the avoidance of complications, and feeling better and more energetic. Negative attitudes were much more frequently discussed and include "technical concerns": anxiety about the pain, proper techniques, and general hassles of taking injections; about hypoglycemic symptoms; and about insulin causing serious health problems; and "experimental concerns": sensing that the disease has progressed into a serious phase, that past treatment efforts have failed, and that the patient has not taken proper care. Attitudes were based on personal experience, observation, what others say, and interactions with health care professionals.
Results from the few published reports on NIDDM patients' attitudes about insulin from various cultural settings were consistent with our findings, indicating that these themes may be generally applicable to a wider population. It is recommended that health care providers take care to avoid unwitting promotion of negative attitudes toward insulin and actively elicit and respond to patient attitudes to reduce reluctance to take the medication.
Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. It is administered subcutaneously.
Reviparin 7000 to 12 600 anti-XalU/day was found to be as effective as intravenous unfractionated heparin in preventing the clinical recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1 large randomised, multi-centre trial (COLUMBUS) and was significantly more effective than intravenous unfractionated heparin in the prevention of recurrent venous thromboembolism in another large randomised, multicentre trial (CORTES). Reviparin has also been compared with unfractionated heparin in children with established DVT. However, the trial was under-powered and no conclusion could be made regarding comparative efficacy.
As prophylaxis, reviparin 1750 anti-XalU once daily was as effective as unfractionated heparin 5000IU twice daily in 1311 patients undergoing abdominal surgery and, in a once daily dosage of 4200 anti-XalU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1750 anti-XalU also effectively prevented DVT, compared with no treatment, in patients undergoing knee arthroscopy. It was also more effective than placebo in patients with brace immobilisation of the lower extremity. Reviparin was compared with ’standard care’ in children with central venous lines. However, the trial was too small to make conclusions regarding its efficacy.
Comparative data indicate that reviparin is at least as well tolerated as heparin and enoxaparin sodium. However, in a large (n = 1279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. The most commonly reported adverse events in therapeutic trials have been intraoperative blood loss and postoperative bleeding complications such as wound haematoma, bruising and injection site haemorrhage. Reviparin was also well tolerated in 2 studies in children aged ≤16 years.
Conclusion: Reviparin has shown efficacy in the treatment of established DVT and in the prevention of postoperative DVT after moderate and high risk surgery and was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip replacement surgery. As an effective and well tolerated antithrombotic agent, reviparin is likely to assume a significant role in the treatment and prevention of DVT, as it appears to have a preferable tolerability profile to subcutaneous heparin after moderate risk surgery and is at least as effective as intravenous heparin in the treatment of established DVT.
Pharmacodynamic Properties
Reviparin (reviparin sodium), a low molecular weight heparin (LMWH) manufactured by cleavage of unfractionated heparin (hereinafter referred to as heparin) with nitrous acid and subsequent Chromatographic purification, has a mean molecular weight of 4400D and a mean peak molecular weight of 3900D. Reviparin catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. However, in addition to a direct effect, the drug’s actions may be modulated by other factors such as tissue factor pathway inhibitor (TFPI). Preclinical and clinical studies have shown that reviparin, like other LMWHs and heparin, stimulates the release of TFPI from endothelial cells, thereby increasing the rate of inactivation of factor Xa and the thromboplastin-factor VIIa complex.
Reviparin has a higher anti-Xa/IIa ratio than heparin and the anti-Xa activity appears to last longer: anti-Xa activity in rabbits dissipated within 2 to 3 hours after intravenous administration of heparin compared with >6 hours after reviparin. After subcutaneous administration of reviparin 40 to 80 anti-XaIU/kg in 10 healthy volunteers, anti-Xa activity increased gradually, reaching a peak after 90 to 150 minutes, before returning to baseline levels within 6 to 8 hours.
Intravenous reviparin produced dose-dependent antithrombotic and anticoagulant effects in a rabbit model of stasis thrombosis. The anticoagulant activity of heparin is conventionally measured using the activated partial thromboplastin time (aPTT), a measure of the intrinsic pathway of blood coagulation. However, unlike heparin, reviparin has minimal effects on the aPTT at prophylactic or therapeutic doses. Therefore, aPTT measurement is not useful for monitoring reviparin.
Reviparin produced a dose-dependent increase in blood loss at dosages that were proportionally higher than those used to assess the antithrombotic actions of the drug after both intravenous and subcutaneous administration in a rabbit ear blood loss model.
Coadministration of oral aspirin 300mg with subcutaneous reviparin (6300 anti-XalU) for 3 days in 9 healthy volunteers significantly prolonged the bleeding time compared with reviparin alone, although this was not thought to be clinically significant.
In a study in 12 healthy volunteers, protamine chloride (given in a 1: 2 ratio with reviparin and 1.2: 1 ratio with heparin) completely neutralised the anti-Xa activity of heparin but reduced the anti-Xa activity of reviparin by only 20 to 40%.
Pharmacokinetic Profile
The pharmacokinetic profile of reviparin administered subcutaneously is characterised by rapid absorption, high bioavailability (≥90%), slow elimination [half life (t1/2β) of 2.5 to 4.3 hours) and dose-independent clearance (⁈1.2 L/h). Maximum plasma anti-Xa activity was reached within 2 to 3.5 hours irrespective of dose.
The area under the plasma anti-Xa activity-time curve (AUC0-24h) was significantly lower with reviparin than with enoxaparin sodium (2.44 vs 3 IU/ml · h, p < 0.05) after adjustment for in vitro anti-Xa activity.
In 10 patients with severe renal failure, t1/2β (5 vs 3.3 hours), mean residence time (8.6 vs 6.5 hours) and the apparent volume of distribution (0.13 vs 0.08 L/kg) of reviparin were significantly higher than those reported in 6 healthy volunteers. Elimination of the drug did not differ to a large extent between interdialysis (t1/2β = 5h) and dialysis periods when dialysis was conducted with high or low permeability membranes (t1/2β = 3.6 vs 4.7h). Mean pharmacokinetic parameters were unchanged in elderly patients.
In children aged 3 days to 16 years with central venous lines, the level of anti-Xa activity in patients weighing ≥5kg peaked (average 0.25 anti-XaIU/ml) 2 hours after administration of reviparin 30 anti-XaIU/kg twice daily. Patients weighing <5kg received reviparin 50 anti-XaIU/kg twice daily and the level of anti-Xa activity (average 0.27 anti-XaIU/ml) peaked 1 to 4 hours after treatment.
Therapeutic Efficacy
Treatment of Established Venous Thromboembolism In 1021 patients (the COLUMBUS trial) with acute symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) or both, fixed dose subcutaneous reviparin (7000 to 12 600 anti-XalU/day dose-adjusted according to 3 body-weight categories) was found to be as effective as adjusted dose intravenous heparin. Of the 510 patients receiving reviparin, 27 (5.3%) had episodes of documented recurrent venous thromboembolism over the 12-week period. Similarly, among the 511 patients treated with heparin, 25 (4.9%) had documented episodes. The majority of the recurrent venous thromboembolic and major bleeding events occurred during the first 14 days of treatment. There were no episodes of fatal bleeding during the trial but 3 patients from each treatment group, each of whom presented with PE, had fatal episodes of PE.
In contrast, results from the CORTES study show that subcutaneous reviparin (7000 to 12 600 anti-XalU/day dose-adjusted according to 3 bodyweight categories) was significantly more effective than intravenous heparin (dose-adjusted to achieve aPTT values between 1.5 and 2.5 times baseline) in preventing the clinical recurrence of DVT and/or PE (in patients with confirmed DVT). Significantly more patients in the reviparin twice daily (53.5%) and reviparin once daily (53.9%) groups experienced thrombus regression, compared with patients in the heparin group (40.8%).
Reviparin has been compared with heparin in the treatment of venous thromboembolism in children aged ≤16 years and >60 days in a randomised, nonblind (with blinded outcome assessment), multicentre trial. Among reviparin recipients, 2 of 37 (5.4%) had an episode of recurrent venous thromboembolism, compared with 5 of 41 (12.2%) patients who received heparin.
Prophylaxis of Venous Thromboembolism The efficacy of subcutaneous reviparin in the prevention of thromboembolism after surgery has been examined in a noncomparative dose-finding study, a comparison with no treatment (after knee arthroscopy) and in randomised, double-blind or single-blind comparisons with placebo, enoxaparin sodium, subcutaneous heparin or acenocoumarol. It has also been compared with “standard care” in the prevention of DVT in children aged ≤16 years with central venous lines in a randomised, nonblind (with blinded outcome assessment), multicentre study.
Reviparin 1750 anti-XalU was significantly more effective than placebo in the prevention of DVT in patients immobilised with a cast after lower extremity fracture or rupture of the Achilles tendon.
In a trial in 1311 patients undergoing abdominal surgery, reviparin 1750 anti-XalU administered 2 hours before surgery and once daily for ≥5 days after surgery was as effective as subcutaneous heparin 5000IU twice daily.
In high risk patients, preliminary dose-finding work showed that a once daily subcutaneous injection of reviparin 4200 anti-XaIU, initiated 10 to 12 hours before hip replacement surgery, completely prevented the development of postoperative DVT. Furthermore, in a large randomised, multicentre trial, a once daily subcutaneous dosage of reviparin 4200 anti-XalU was as effective as a once daily subcutaneous dosage of enoxaparin sodium 40mg in patients undergoing total hip replacement surgery. Additionally, in a large (n = 1279) study in patients after undergoing total hip replacement surgery, the cumulative failure rate of therapy (the combined incidence of a confirmed symptomatic thromboembolic event, a major bleed, or death) over the 6-week period after surgery was significantly in favour of reviparin compared with acenocoumarol (3.7% vs 8.3%, p = 0.001).
Reviparin also effectively prevented DVT in patients undergoing knee arthroscopy, compared with no treatment, in a randomised, nonblind (with blinded outcome assessment), single-centre trial. Among 117 patients randomised to receive reviparin 1750 anti-XalU/day, 1 (0.9%) developed DVT, compared with 5 (4.1%) patients who received no treatment. There was no incidence of PE in either group.
Reviparin was also effective in the prophylaxis of venous thromboembolism during pregnancy in patients with a history of venous thromboembolism.
In children aged ≤16 years with central venous lines, 11 of 78 (14.1%) reviparin recipients (30 anti-XaIU/kg twice daily) developed DVT compared with 10 of the 80 (12.5%) patients who received “standard care”. Three patients in each group had symptomatic DVT, and of the 7 patients aged between 0 and 3 months, 3 experienced DVT.
Tolerability
Clinical trials have shown that subcutaneous reviparin is well tolerated when used for the prophylaxis and treatment of thromboembolism. Comparative data indicate that its tolerability profile is at least as good as those of intravenous heparin and subcutaneous enoxaparin sodium. Furthermore, long term use of reviparin (≤6 weeks) was well tolerated in 2 studies.
In patients undergoing abdominal surgery, reviparin was associated with significantly fewer postoperative bleeding complications, such as wound haematoma, bruising and injection site haemorrhage, than heparin. However, there were no statistically significant between-group differences in episodes of peri- and postoperative blood loss or blood transfusion requirements.
In patients undergoing total hip replacement surgery, reviparin was associated with slightly fewer haematomas and bruisings than enoxaparin sodium, although the differences did not reach statistical significance. However, in a large (n = 1279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. Furthermore, there were no episodes of major bleeding in 2621 immobilised outpatients who self-administered reviparin 1750 anti-XalU for 1 to 4 weeks; 4% of patients experienced injection site haemorrhage and minor bleeding events occurred in 9%.
In a small trial involving 158 children with central venous lines, no patients who received reviparin 30 anti-XaIU/kg twice daily for 30 days experienced major bleeding, compared with 1 patient who received “standard care”.
Bleeding complications tend to be less frequent in nonsurgical patients with established DVT than in surgical patients. There was no statistically significant difference between the number of episodes of major or minor bleeding in patients receiving reviparin or intravenous heparin.
As yet, there have been no reports of reviparin-induced osteoporosis. Limited data suggest the drug may be well tolerated during pregnancy but this has to be confirmed.
In a small trial involving 78 children with established venous thromboembolism, major bleeding complications occurred in 3 of 37 (8.1%) patients who received reviparin 100 anti-XaIU/kg twice daily for 3 months, compared 5 of 41 (12.2%) heparin recipients.
Dosage and Administration
Reviparin is approved for the prevention of DVT and PE in patients at moderate risk (i.e. general surgery) and high risk (i.e. orthopaedic surgery), for the treatment of venous thromboembolism and for anticoagulation during haemodialysis and extracorporeal circulation. The recommended injection site is in the skin of the abdominal wall, between the umbilicus and iliac crest, or on the front of the thigh. Because of the risk of provoking wound haematomas, reviparin should not be administered intramuscularly.
The recommended dosage for the prophylaxis of DVT in patients undergoing moderate risk surgery (i.e. abdominal surgery) is a subcutaneous injection of reviparin 0.25ml (1750 anti-XalU) initially administered 2 hours prior to surgery and continued once daily until the patient is fully mobile.
For high risk surgical patients (i.e. those undergoing orthopaedic surgery) a once daily subcutaneous injection of reviparin 0.6ml (4200 anti-XalU), initiated 12 hours before surgery, is recommended for the prophylaxis of DVT.
Treatment of established DVT involves a twice daily subcutaneous injection of reviparin, dose-adjusted according to 3 bodyweight categories, with concomitant treatment with an oral anticoagulant.
Prophylaxis or treatment with reviparin does not require the monitoring of aPTT values. However, in elderly patients and patients with renal insufficiency, monitoring of the anti-Xa levels is recommended because of possible delayed elimination of the drug. Anti-Xa monitoring in pregnant patients is also recommended because of the bodyweight increase over the course of the pregnancy.
The evaluation of the efficacy of medication is confounded when patients do not adhere to prescribed regimens. Overdosing, underdosing, and erratic dosing intervals can diminish drug action or cause adverse effects. Using a new method with epilepsy as a model, we assessed compliance with long-term medications among newly treated and long-term patients. Medication Event Monitor Systems (Aprex Corporation, Fremont, Calif) are standard pill bottles with microprocessors in the cap to record every bottle opening as a presumptive dose. Compliance rates averaged 76% during 3428 days observed: 87% of the once daily, 81% of the twice daily, 77% of the three times a day, and 39% of the four times a day dosages were taken as prescribed. Coefficients of variation of drug serum concentrations had no significant relationship to compliance rates. Pill counts overestimated compliance increasingly as compliance with the prescribed regimen declined. Neither drug serum concentrations nor pill counts would have identified the frequency of missed doses that were revealed with continuous dose observations.(JAMA. 1989;261:3273-3277)
Venous thromboembolism (VTE) represents a significant preventable cause of hospital mortality. VTE assessment and prophylaxis rates are key patient safety and quality of care indicators. The aim of this study was to audit low molecular weight heparin (LMWH) and graduated elasticated compression stockings (GECS) prescriptions compared with the current Clinical Guidelines for Operations.
Complete audit loop in the Role 3 Hospital, Camp Bastion, Afghanistan. A multifaceted intervention programme incorporating physician and nurse education and pre-printed medication charts was introduced to improve VTE assessment and prophylaxis rates.
Only 111/301 (36.9%) of patients in the pre-intervention cohort had a VTE risk assessment performed; this improved to 142/155 (91.6%, p<0.0001) post-intervention. A total of 57/88 (64.8%) patients prescribed LMWH pre-intervention had a documented assessment of bleeding risk performed; this rose to 65/66 (98.5%, p=0.0003) post-intervention. In pre-intervention, only 63/213 (29.6%) patients had a documented reassessment of VTE and bleeding risk at 24 h; reassessment rates rose to 68.8% (66/96 patients, p<0.0001) post-intervention. Of those patients at risk of VTE without ongoing bleeding risk, 62/96 (64.6%) had LMWH prescribed pre-intervention; this rose to 57/62 (91.9%) post-intervention (p<0.0001). Inappropriate LMWH prescription rates fell from 26/190 (13.7%) to 4/85 (4.7%, p=0.035) post-intervention. In those patients in whom GECS were not contraindicated, prescription rates rose from 23/95 (24.2%) to 42/62 (67.7%, p<0.0001) post-intervention.
Inclusion of pre-printed LMWH/GECS prescriptions and risk assessment stickers in the mediction chart significantly improved rates of VTE risk assessment and prophylaxis. These easily reproducible and low-cost interventions could improve patient safety on deployment.
Die Gipsimmobilisation nach Unfalltrauma an der unteren Extremität beinhaltet ein besonderes Risiko für die Thrombogenese.
In einer prospektiv, kontrolliert und randomisiert durchgeführten Studie wurde eine Gruppe ambulanter, konservativ im Unterschenkelgips
oder Oberschenkelgipstutor behandelter Patienten mit einmal täglicher Injektion eines niedermolekularen Heparins (n=176) mit
einer Patientengruppe ohne Thromboseprophylaxe (n=163) verglichen. In der Gruppe ohne Behandlung mit niedermolekularem Heparin
wurden bei sieben Patienten tiefe Beinvenenthrombosen (=4,3%) festgestellt gegenüber keiner Beinvenenthrombose (0%) in der
mit niedermolekularem Heparin behandelten Gruppe (p=0,006). Ernsthafte Nebenwirkungen der Prophylaxe traten nicht auf. Die
subkutanen Injektionen des niedermolekularen Heparins in Fertigspritzen wurden von 89% der Männer und 72% der Frauen selbst
durchgeführt. Das Risiko tiefer Beinvenenthrombosen bei den Patienten der Prophylaxegruppe wurde effektiv gemindert.
Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled,
randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively
treated outpatients with plaster cast immobilisation of the leg (n=163 control group without prophylaxis). By application
of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n=176) was reduced
to 0% (p=0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated
by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective
to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg.
Eine routinemige Thromboseprophylaxe ist fester Bestandteil der chirurgischen Behandlung. Die Indikationsstellung und Wahl der Prophylaxeform erfolgen in Abhngigkeit vom individuellen Risikoprofil des Patienten, welches durch Kombination von expositionellen und dispositionellen Risikofaktoren bestimmt wird. Das expositionelle Risiko ist durch Art und Umfang des chirurgischen Eingriffs bzw. Traumas geprgt, wogegen das dispositionelle Risiko patientenbezogene Risikofaktoren beinhaltet. In der nachfolgenden bersicht wird ein berblick ber die aktuellen Prophylaxemethoden, ihre pharmakologischen Details und ihre klinische Relevanz gegeben. Vor dem Hintergrund evidenzbasierter Daten und der Empfehlungen der Fachgesellschaften wird auch zur Dauer der Prophylaxe und zu forensischen Fragen Stellung bezogen. Die Entwicklung neuer Medikamente vergrert die Bandbreite der Prophylaxeprinzipien und schafft neuen Informationsbedarf.Prophylactic treatment against deep vein thrombosis has become a routine part of surgical treatment. The indications and the form of prophylaxis selected depend on the patients individual risk profile, which is determined in turn by a combination of exposing and predisposing risk factors. The exposing risk factors depend on the type of surgery and trauma the patient is exposed to, while the predisposing risks are determined by factors peculiar to the patient. This review deals with the modalities of prophylaxis currently available, pharmacological details relating to these, and their clinical significance. In addition, evidence-based data, recommendations for the duration of prophylaxis derived from official guidelines, and medicolegal aspects are discussed. The development of new anticoagulants is expanding the range of prophylactic methods, which means further information is needed.
Background: Low molecular weight heparin (LMWH) as daily injection is an essential tool for effective prophylaxis against deep vein thrombosis
(DVT) today. Daily self-injection by the patients or their families is common practice. The effectiveness of this measure
depends on a high patient compliance. The intention of this study was to explore the rate of patients incompliant with LMWH
self-injection according to an anonymous questionnaire.
Patients and Methods: Following knee arthroscopy, data of 207 patients were collected concerning knowledge of DVT, acceptance and compliance with
self-injection.
Results: In 16 cases (7.7%), self-injection was rejected, and the injections were given by a nursing service. Of the remaining patients,
160 (77.3%), administered the injections themselves, in 31 patients (15%) members of the family were involved. Only 81.2%
of these patients would prefer self-injection in the same situation. Problems with self-injection were seen in 34.8% initially
and in 6.3% the whole time. In 54 cases (28.3%), LMWH prophylaxis was not sure. This was due to the forgetting of single injections
or an early termination of the therapy. Most importantly, all patients < 20 years had an uncertain prophylaxis.
Conclusions: The compliance with the self-injection of LMWH depends on the knowledge of DVT problems, rating of the individual DVT risk,
and general perception of injections. The results of this study show a lower compliance with an acceptance of self-injection
than generally postulated. Given the importance of an effective DVT prophylaxis with LMWH, a nursing service should be involved
in case of any doubt about outpatient compliance.
Prevention of venous thromboembolism has become routine in all surgical disciplines and consists of physical and pharmacological measures. The indications and choice of prophylaxis modality depend on the individual patient risk profile which is determined by the combination of exposing and predisposing risk factors. The exposing risk factors are characterized by the type and extent of surgery or trauma, whereas the predisposing risk factors relate to patient-inherent risk factors. This is also taken into consideration for the compilation of guidelines. This review summarizes the recommendations of the German S3 guidelines related to surgery and also discusses the perioperative management of patients receiving long-term anticoagulation with new oral anticoagulants (rivaroxaban, apixaban, dabigatran).
Thromboembolic disease presents a potentially fatal complication to patients undergoing orthopaedic surgery. Although the incidence after hip and knee surgery has been studied and documented, its incidence after surgery of the foot and ankle is unknown. For this reason, a prospective multicenter study was undertaken to identify patients with clinically evident thromboembolic disease to evaluate potential risk factors. Two thousand seven hundred thirty-three patients were evaluated for preoperative risk factors and postoperative thromboembolic events. There were six clinically significant thromboembolic events, including four nonfatal pulmonary emboli, after foot and ankle surgery. The incidence of deep vein thrombosis was six of 2733 (0.22%) and that of nonfatal pulmonary emboli was four of 2733 (0.15%). Factors found to correlate with an increased incidence of deep vein thrombosis were nonweightbearing status and immobilization after surgery. On the basis of these results, routine prophylaxis for thromboembolic disease after foot and ankle surgery probably is not warranted.
(C) Lippincott-Raven Publishers.
The incidence of venous thromboembolism after elective knee surgery has previously been studied almost exclusively in patients receiving total knee replacements, in whom the risk of a deep vein thrombosis is approximately 60%. We report the results of ipsilateral ascending venography in 312 patients undergoing a wide variety of elective knee operations under tourniquet ischaemia, none of whom received any specific prophylaxis against thromboembolism. Total knee replacement was confirmed to carry a high risk with ipsilateral deep vein thrombosis in 56.4% and symptomatic pulmonary embolism in 1.9%. By contrast, arthroscopy was associated with a low incidence of venous thrombosis (4.2%). Meniscectomy, arthrotomy, patellectomy, synovectomy and arthrodesis were all high-risk procedures, particularly in patients over 40 years of age, and were associated with deep vein thrombosis rates of 25% to 67%. On the basis of these findings, we advise prophylaxis against venous thromboembolism in all patients over 40 years of age undergoing elective knee surgery other than arthroscopy.
Plaster cast immobilisation following trauma is a major risk factor for the development of deep vein thrombosis. In our controlled, randomized and prospective study in patients with minor injuries the incidence of deep vein thrombosis was 4.3% in conservatively treated outpatients with plaster cast immobilisation of the leg (n = 163 control group without prophylaxis). By application of low molecular weight heparin once daily the number of deep vein thrombosis in the prophylaxis group (n = 176) was reduced to 0% (p = 0.006). No severe side effects of low molecular weight heparin were observed. Subcutaneous injections were self-applicated by 89% of males and 72% of females. We conclude that thromboprophylaxis with low molecular weight heparin once daily is effective to reduce the risk of deep vein thrombosis in outpatients with plaster cast immobilisation of the leg.
Deep vein thrombosis (DVT) with subsequent pulmonary emboli (PE) is the most life-threatening complication of knee arthroscopy. Although the incidence of clinically diagnosed DVT after arthroscopy is low, clinical examination is less sensitive and specific than other diagnostic modalities for the detection of venous clot. This study used compression ultrasound to prospectively evaluate patients before and after arthroscopic surgery for the presence of DVT. Preoperatively, patients were screened for DVT risk factors. Eighty-five patients completed the study. Three asymptomatic "silent" DVTs were identified, for an incidence of 3.5%. There was no statistically significant difference between those with and without risk factors for the development of DVT.
Hypoglycemia is a common stressful occurrence for people with type I diabetes, is disruptive to daily activities, and is a source of embarrassment, fear, and anxiety. Adequate knowledge about hypoglycemia is needed to recognize, treat, and prevent this condition. Families and friends also need adequate knowledge about hypoglycemia to provide helpful support. In this study, the Hypoglycemia Knowledge Questionnaire was used to measure knowledge about hypoglycemia in a convenience sample of 94 young women with type I diabetes and 94 supportive others. Knowledge about hypoglycemia was significantly higher for the young women with diabetes than for their supportive others, although knowledge deficits were evident for the young women on selected questionnaire items. Because normalization of blood glucose is associated with an increased risk of hypoglycemia, comprehensive evaluation of knowledge about hypoglycemia is critical to self-care. Additional studies are needed to validate the reliability and evaluate the usefulness of the Hypoglycemia Knowledge Questionnaire in clinical and research applications.
Hypoglycemia is a relatively common experience for people with type I diabetes, occurring in response to seemingly minor alterations in the usual routine of diet, exercise, and insulin. Even before the results of the Diabetes Control and Complications Trial ¹ were known, young women with diabetes were considered candidates for tight control in anticipation of conception. All people with type I diabetes receiving intensive insulin therapy to normalize blood glucose face a significantly increased risk of hypoglycemia. Knowledge about hypoglycemia and its management are essential to minimize the adverse effects of insulin therapy and increase success with achieving target blood glucose levels. Prompt recognition and treatment of hypoglycemia by persons with type I diabetes and their supportive others depends on knowledge about hypoglycemia and is essential to reversing this condition.
Knowledge deficits among adults with diabetes as well as among children with diabetes and their parents have been well documented in the literature. 2–13 Thorough examination reveals that only a small number of items on knowledge tests assessed hypoglycemia knowledge per se. These items did not allow for adequate evaluation of the full breadth and depth of content recommended for hypoglycemia education for people with type I diabetes and their supportive others. 14,15
Because of the comprehensive nature of recommendations for hypoglycemia education and the lack of adequate evaluation in this content area, a thorough examination of the hypoglycemia knowledge of young women with type I diabetes and their supportive others was undertaken as part of a larger correlational study on social support and hypoglycemia. The findings reported here are related to two study questions: 1) What is the level of hypoglycemia knowledge among young women with type I diabetes and their supportive others? and 2) What is the relationship between hypoglycemia knowledge of young women with diabetes and that of their supportive others?
To evaluate the impact of dosage frequency on the compliance of patients who receive their medicines from community pharmacies.
Each month, patients received a supply of their medication in a Medication Event Monitoring Systems container, which registered each opening of the package. At the end of the study, the patients received a short questionnaire. The subjects were 91 diabetic patients using oral antidiabetic agents. Patients taking insulin and those who were unable to collect their medicines from the pharmacy were excluded from the study. Compliance was defined as the percentage of doses taken during the observation period. Another parameter used was compliance with the prescribed regimen, defined as the percentage of days in which the number of tablets were taken as prescribed. As a last parameter, compliance with the prescribed dose intervals was used.
Compliance is influenced by the frequency of doses. The compliance for this group of patients is 74.8%, with an average of 79% in the case of a dose once daily and 38% in the case of a dose three times daily. The predominant type of noncompliance in all groups was dose omissions. However, more than one-third of the patients used more doses than prescribed. Overconsumption is a frequently made mistake by patients on a one-dose daily schedule.
The reduction of dose frequency may decrease total noncompliance, but at the same time, it increases the risk of overconsumption. Reducing the frequency does not automatically result in a better therapeutic schedule. The choice of once or twice daily should depend on the therapeutic range of the drug.
Unlabelled:
Reviparin (reviparin sodium) is a low molecular weight heparin (LMWH) that catalyses the inactivation of factors Xa and IIa by binding to antithrombin, which ultimately leads to the inhibition of the clotting cascade. It is administered subcutaneously. Reviparin 7,000 to 12,600 anti-XaIU/day was found to be as effective as intravenous unfractionated heparin in preventing the clinical recurrence of acute deep vein thrombosis (DVT) and/or pulmonary embolism in 1 large randomised, multicentre trial (COLUMBUS) and was significantly more effective than intravenous unfractionated heparin in the prevention of recurrent venous thromboembolism in another large randomised, multicentre trial (CORTES). Reviparin has also been compared with unfractionated heparin in children with established DVT. However, the trial was under-powered and no conclusion could be made regarding comparative efficacy. As prophylaxis, reviparin 1,750 anti-XaIU once daily was as effective as unfractionated heparin 5,000IU twice daily in 1,311 patients undergoing abdominal surgery and, in a once daily dosage of 4,200 anti-XaIU, was as effective as subcutaneous enoxaparin sodium 40 mg/day or acenocoumarol in patients undergoing hip replacement surgery. Reviparin 1,750 anti-XaIU also effectively prevented DVT. compared with no treatment, in patients undergoing knee arthroscopy. It was also more effective than placebo in patients with brace immobilisation of the lower extremity. Reviparin was compared with 'standard care' in children with central venous lines. However, the trial was too small to make conclusions regarding its efficacy. Comparative data indicate that reviparin is at least as well tolerated as heparin and enoxaparin sodium. However, in a large (n = 1,279) trial there were significantly fewer major bleeding episodes in patients receiving reviparin than in patients given the oral anticoagulant acenocoumarol. The most commonly reported adverse events in therapeutic trials have been intraoperative blood loss and postoperative bleeding complications such as wound haematoma, bruising and injection site haemorrhage. Reviparin was also well tolerated in 2 studies in children aged < or = 16 years.
Conclusion:
Reviparin has shown efficacy in the treatment of established DVT and in the prevention of postoperative DVT after moderate and high risk surgery and was as effective as enoxaparin sodium or acenocoumarol in patients undergoing hip replacement surgery. As an effective and well tolerated antithrombotic agent, reviparin is likely to assume a significant role in the treatment and prevention of DVT, as it appears to have a preferable tolerability profile to subcutaneous heparin after moderate risk surgery and is at least as effective as intravenous heparin in the treatment of established DVT.
Prophylactic treatment against deep vein thrombosis has become a routine part of surgical treatment. The indications and the form of prophylaxis selected depend on the patient's individual risk profile, which is determined in turn by a combination of exposing and predisposing risk factors. The exposing risk factors depend on the type of surgery and trauma the patient is exposed to, while the predisposing risks are determined by factors peculiar to the patient. This review deals with the modalities of prophylaxis currently available, pharmacological details relating to these, and their clinical significance. In addition, evidence-based data, recommendations for the duration of prophylaxis derived from official guidelines, and medicolegal aspects are discussed. The development of new anticoagulants is expanding the range of prophylactic methods, which means further information is needed.
Komplika-tionsanalyse und Strategien zur Komplikationsre-duktion bei der Kniegelenksarthroskopie. Arthro-skopie
- J Grifka
- C Knaup
- Salewsky
Grifka J, Knaup C, Salewsky G (1995) Komplika-tionsanalyse und Strategien zur Komplikationsre-duktion bei der Kniegelenksarthroskopie. Arthro-skopie:105–110
Thrombosis prophylaxis in surgery. What is the evidence?
- Haas
Implementing ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity
- H J Kock
- K P Schmit-Neuerburg
- J Hanke
- Kock
Komplikationsanalyse und Strategien zur Komplikationsreduktion bei der Kniegelenksarthroskopie
- J Grifka
- C Knaup
- G Salewsky
Venous thromboembolism: reducing the risk
- Excellence Nifhac
Incidence of deep vein thrombosis after arthroscopic knee surgery: a prospective study
- J S Williams
- M J Hulstyn
- P D Fadale
- Williams
Thrombosis prophylaxis in surgery. What is the evidence?
- S Haas
- A Encke
- R Krauspe
- Haas